Background: Mutations in the cardiac troponin T gene causing familial hyper
trophic cardiomyopathy (HCM) are associated with a very poor prognosis but
only mild hypertrophy. To date, the serial morphologic changes in patients
with HCM linked to cardiac troponin T gene mutations have not been reported
Hypothesis: The aim of this study was to determine the long-term course of
patients with familial HCM caused by the cardiac troponin T gene mutation,
Methods: In all, 140 probands with familial HCM were screened for mutations
in the cardiac troponin T gene.
Results: The Arg92Trp missense mutation was present in 10 individuals from
two unrelated pedigrees. They exhibited different cardiac morphologies: thr
ee had dilated cardiomyopathy- like features, five had asymmetric septal hy
pertrophy with normal left ventricular systolic function, one had electroca
rdiographic abnormalities without hypertrophy, and one had the disease-caus
ing mutation but did not fulfill the clinical criteria for the disease. The
mean maximum wall thickness was 14.1 +/- 6.0 mm. The three patients with d
ilated cardiomyopathy-like features had progressive left ventricular dilati
on. Three individuals underwent right ventricular endomyocardial biopsy. Th
ere was a modest degree of myocardial hypertrophy (myocyte diameter: 18.9 /- 5.2 mum), and minimal myocardial disarray and mild fibrosis were noted.
Conclusion: The Ag92Trp substitution in the cardiac troponin T gene shows a
high degree of penetrance, moderate hypertrophy, and early progression to
dilated cardiomyopathy in Japanese patients. Early identification of indivi
duals with this mutation may provide the opportunity to evaluate the effica
cy of early therapeutic interventions.